AUTHOR=Sharghi Shirin , Flunkert Stefanie , Daurer Magdalena , Rabl Roland , Chagnaud Boris Philippe , Leopoldo Marcello , Lacivita Enza , Hutter-Paier Birgit , Prokesch Manuela 

TITLE=Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1087788

DOI=10.3389/fnins.2023.1087788

ISSN=1662-453X

ABSTRACT=<sec><title>Introduction</title><p>Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by two core behavioral symptoms: impaired social communication and interaction, as well as stereotypic, repetitive behavior. No distinct cause of ASD is known so far; however, excitatory/inhibitory imbalance and a disturbed serotoninergic transmission have been identified as prominent candidates responsible for ASD etiology.</p></sec><sec><title>Methods</title><p>The GABA<sub><italic>B</italic></sub> receptor agonist R-Baclofen and the selective agonist for the 5HT<sub>7</sub> serotonin receptor LP-211 have been reported to correct social deficits and repetitive behaviors in mouse models of ASD. To evaluate the efficacy of these compounds in more details, we treated BTBR <italic>T<sup>+</sup> Itpr3<italic><sup>tf</sup></italic>/J</italic> and B6.129P2-<italic>Fmr1</italic><sup><italic>tm</italic>1<italic>Cgr</italic></sup>/<italic>J</italic> mice acutely with R-Baclofen or LP-211 and evaluated the behavior of animals in a series of tests.</p></sec><sec><title>Results</title><p>BTBR mice showed motor deficits, elevated anxiety, and highly repetitive behavior of self-grooming. <italic>Fmr1</italic>-KO mice exhibited decreased anxiety and hyperactivity. Additionally, <italic>Fmr1</italic>-KO mice’s ultrasonic vocalizations were impaired suggesting a reduced social interest and communication of this strain. Acute LP-211 administration did not affect the behavioral abnormalities observed in BTBR mice but improved repetitive behavior in <italic>Fmr1</italic>-KO mice and showed a trend to change anxiety of this strain. Acute R-Baclofen treatment improved repetitive behavior only in <italic>Fmr1</italic>-KO mice.</p></sec><sec><title>Conclusion</title><p>Our results add value to the current available data on these mouse models and the respective compounds. Yet, additional studies are needed to further test R-Baclofen and LP-211 as potential treatments for ASD therapy.</p></sec>